WO2006028277A1 - A pharmaceutical composition for treating ataxia, multiple system atrophy or balance disorders - Google Patents
A pharmaceutical composition for treating ataxia, multiple system atrophy or balance disorders Download PDFInfo
- Publication number
- WO2006028277A1 WO2006028277A1 PCT/JP2005/016994 JP2005016994W WO2006028277A1 WO 2006028277 A1 WO2006028277 A1 WO 2006028277A1 JP 2005016994 W JP2005016994 W JP 2005016994W WO 2006028277 A1 WO2006028277 A1 WO 2006028277A1
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- WO
- WIPO (PCT)
- Prior art keywords
- compound
- ataxia
- compounds
- solvate
- improving
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- 0 CC(C(C(NC(Cc1c[s]cn1)C(N1C(*)CCC1)=O)=O)N1)OC1=O Chemical compound CC(C(C(NC(Cc1c[s]cn1)C(N1C(*)CCC1)=O)=O)N1)OC1=O 0.000 description 1
- RVAFDUBAJVHJOG-UHFFFAOYSA-N CN(C(CCN1)=O)C1=O Chemical compound CN(C(CCN1)=O)C1=O RVAFDUBAJVHJOG-UHFFFAOYSA-N 0.000 description 1
- ZWNLHORVRPWOBP-WODVXLOZSA-N C[C@@H](CCC1)N1C([C@@H](CC1N=CNC1)NC([C@H](CC1)NC1=O)=O)=O Chemical compound C[C@@H](CCC1)N1C([C@@H](CC1N=CNC1)NC([C@H](CC1)NC1=O)=O)=O ZWNLHORVRPWOBP-WODVXLOZSA-N 0.000 description 1
- ZQNYZRQMLWZVFU-NXEZZACHSA-N NC([C@@H](CCC1)N1C([C@@H](Cc1c[nH]cn1)NC=O)=O)=O Chemical compound NC([C@@H](CCC1)N1C([C@@H](Cc1c[nH]cn1)NC=O)=O)=O ZQNYZRQMLWZVFU-NXEZZACHSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Definitions
- the present invention relates to a pharmaceutical composition for treating spinocerebellar ataxia (or atrophy, degeneration) or multiple system atrophy, or for improving ataxia or equilibrium disturbance.
- SCA Spinocerebellar ataxia
- cerebellar ataxia includes neurodegeneration diseases in which the main locus of pathological change exists in nucleus or neural pathway of cerebellum, brainstem or spinal cord.
- cerebellar ataxia or posterior column ataxia is shown.
- SCA is classified into hereditary diseases such as hereditary olivo-ponto-cerebellar atrophy, hereditary cortical cerebellar atrophy, Machado-Joseph disease, Friedreich's ataxia, hereditary Dentatorubral pallidoluysian atrophy and the like, and nonheritable diseases such as olivo-ponto-cerebellar atrophy, Shy-Drager syndrome, striato-nigral degeneration, cortical cerebellar atrophy and the like, and critical causes of these diseases have been unknown. Although conditions of diseases and progresses of the condition depend on type of diseases, all of diseases are progressive. The patients are finally confined to their beds and often lead to pulmonitis, asphyxia or sudden death. SCA is neural intractable diseases of unknown causes and investigations of the causes and establishment of an effective method for the treatment have been required.
- hereditary diseases such as hereditary olivo-ponto-cerebellar atrophy, hereditary cortical cerebell
- olivo-ponto-cerebellar atrophy and Shy- Drager syndrome have many common features in pathological findings, they can be classified as multiple system atrophy.
- a definition for classification between spinocerebellar ataxia and multiple system atrophy are indefinite.
- Thyrotropin- releasing hormone is considered to be effective for treating or amelioration of spinocerebellar ataxia, and the compounds described in Patent Literature 1 and Non-Patent Literature 1 are used for a pharmaceutical composition for treating spinocerebellar ataxia.
- TRH Thyrotropin- releasing hormone
- Literature 2 it is described that compounds having TRH- like activity are effective for treating spinocerebellar ataxia and TRH derivatives have been developed as a drug for spinocerebellar ataxia. A more excellent pharmaceutical composition for treating and ameliorating spinocerebellar ataxia has been desired.
- Patent Literature 8 discloses compounds which show activating effect of central nervous system and which are useful for treating various symptoms caused by hypoactivity of dopamine system, norepinephrine system and acetylcholine system.
- the chemical structures of the compounds of the present invention are disclosed.
- Patent Literature 9 discloses that the compounds of the present invention are useful for treating Parkinson's diseases
- Patent Literature 10 discloses that bioavailability (hereinafter referred to as BA) of the compounds are 4 to 34 times higher than that of TRH or TRH derivatives. None of the prior art discloses that the compounds of the present invention have particular effect for treating spinocerebellar ataxia or multiple system atrophy.
- Patent Literature 1 JP 61-33197 A
- Patent Literature 2 JP 63-290876 A
- Patent Literature ⁇ WO98/08867
- Patent Literature9 WO02/17954
- Patent Literature 10 WO99/53941
- Non-Patent Literature 1 European Journal of Pharmacology, 1994, vol. 271, p. 357
- Non-Patent Literature 2 "Asu no Shinyaku, Division of drug efficacy, drugs for neurosystem and sensory organ-2, drugs for central nervous system (vol.2), drugs for peripheral nervous system", Technomics, Inc, published on July 22, 2004, page 409
- the present invention provides a pharmaceutical composition for treating spinocerebellar ataxia (atrophy or degeneration) or multiple system atrophy, or for improving ataxia or equilibrium disturbance .
- the present invention provides
- a pharmaceutical composition for treating spinocerebellar ataxia or multiple system atrophy comprising a compound of the formula (I): wherein R is methyl, cyano or carbamoyl, a pharmaceutically acceptable salt, or a solvate thereof as an active ingredient.
- a pharmaceutical composition for improving ataxia comprising a compound of the formula (I) as described in the above (1), a pharmaceutical acceptable salt, or a solvate thereof as an active ingredient.
- a pharmaceutical composition for improving equilibrium disturbance comprising a compound of the formula (I) as described in the above (1), a pharmaceutical acceptable salt, or a solvate thereof as an active ingredient.
- the compounds of the present invention have an effect for improving ataxia or equilibrium disturbance caused by spinocerebellarataxia or multiple system atrophy, and are useful for a composition for treating spinocerebellar ataxia or multiple system atrophy, or for improving ataxia or equilibrium disturbance .
- Figure 1 shows an effect of Compound (1-1) for improving ataxia (equilibrium disturbance) in rolling mouse Nagoya.
- Figure 2 shows an effect of Compound (1-1) for improving ataxia (equilibrium disturbance) in cerebellum-damaged rat induced by Ara-C.
- Figure 3 shows effects of Compounds (1-3) and (1-4) for improving ataxia
- solvate includes hydrate, solvate with an organic solvent and the like.
- the compound of the present invention may be coordinate with an arbitrary number of water molecules to give hydrate thereof.
- Monohydrate or trihydrate is preferable.
- a suspension of trihydrate in water is easy to handle for mass production because sedimentation rate of trihydrate particles is low.
- the compounds of the present invention include pharmaceutically acceptable salts of each compound.
- Exemplified are salts with an alkaline metal such as lithium, sodium, potassium or the like, salts with alkaline earth metals such as magnesium, calcium and the like, salts with ammonium, salts with an organic base, salts with an amino acid, salts with a mineral acid such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid or the like, and salts with an organic acid such as acetic acid, citric acid, maleic acid, fumaric acid, benzenesu]fonic acid, p- toluenesulfonic acid or the like.
- These salts can be formed by usual manners.
- the compounds of the present invention are not limited to a specific isomer and include all of formable isomers and racemates.
- the compounds of the present invention can be produced by known methods described in Patent Literature 8, Patent Literature 9 and the like.
- Thus-obtained compounds can be changed to a salt or solvate such as hydrate thereof by usual manners.
- the compounds of the present invention have a remarkable effect for improving ataxia (especially, motor ataxia caused by coordination disturbance and equilibrium disturbance) as mentioned below in Experimental Example. Because the compounds of the present invention have improved brain penetration rather than TRH or other TRH derivatives, the small amount of the compounds can show the certain drug efficacy. Moreover, although TRH and other TRH derivatives are easily metabolized in the brain, as the compounds of the present invention have the excellent intracerebral stability. Therefore, the compounds of the present invention are expected to show continuous drug efficacy. As a result, a dosage schedule is easily planned, and dose and frequency of dosage can be decreased. Therefore, the compounds of the present invention can be a preferable drug in consideration of patient's QOL.
- Patent Literature 8 discloses similar compounds to the compounds of the present invention.
- the compounds of the present invention show higher effect for improving ataxia in comparison with the compounds in Patent Literature 8.
- the compounds of the present invention have activities for treating or improving all of diseases and symptoms which are classifiable into spinocerebellar ataxia or multiple system atrophy.
- diseases are hereditary olivo-ponto- cerebellar atrophy, hereditary cerebellar cortical atrophy, Friedreich ataxia, Machado- Joseph diseases, Ramsay Hunt syndrome, hereditary dentatorubral-pallidoluysian atrophy, hereditary spastic paraplegia, olivo-ponto-cerebellar atrophy, Shy-Drager syndrome, cortical cerebellar atrophy, striato-nigral degeneration, Marinesco-Sjogren symdrome, alcoholic cortical cerebellar atrophy, paraneoplasic cerebellar atrophy associated with malignant tumor, toxic cerebellar atrophy caused by toxic substances, cerebellar atrophy associated with endocrine disturbance and the like.
- the symptoms are ataxia such as motor ataxia, trunk ataxia, limb ataxia and the like, autonomic disturbance such as orthostatic hypotension, dysuria, hypohidrosis, sleep apnea, orthostatic syncope and the like., stiffness of lower extremity, ocular nystagmus, oculomotor nerve disorder, pyramidal tract dysfunction, extrapyramidal symptom (postural adjustment dysfunction, muscular rigidity, akinesia, tremulus), dysphagia, lingual atrophy, posterior funiculus symptom, muscle atrophy, muscle weakness, deep hyperrefLexia, sensory disturbance, scoliosis, kyphoscoliosis, foot deformans, anarthria, dementia, manic state, decreased motivation for rehabilitation and the like.
- autonomic disturbance such as orthostatic hypotension, dysuria, hypohidrosis, sleep apnea, orthostatic syncope and the like.
- stiffness of lower extremity ocular nystagmus
- the compounds of the present invention are markedly effective for improvement of ataxia and equilibrium disturbance .
- Ataxia includes spinal ataxia, labyrinthine ataxia, cerebral ataxia and cerebellar ataxia.
- the compounds of the present invention are markedly effective for cerebellar ataxia (for example, motor ataxia caused by coordination disturbance and equilibrium disturbance).
- a compound of the present invention can be administered to a human for treating or improving the above-mentioned diseases and symptoms by oral administration form such as powders, granules, tablets, capsules, pills, solutions and the like or parenteral administration form such as injections, suppositories, endermic agents, vapors and the like.
- a pharmaceutical composition can be prepared by mixing an effective dose of a compound of the present invention with various additives suitable for the administration form, such as excipients, binders, moistening agents, disintegrators, lubricants and the like, if needed.
- a compound together with a suitable carrier can be sterilized to give a pharmaceutical composition.
- Oral administration by pills, capsules, buccals, jelly tablets, solutions and the like are preferable.
- an usual oral dosage for an adult is 0.01 to 100 mg/day and preferable is 0.1 to 40 mg/day, and more preferable is 0.5 to 20 mg/day.
- an usual dosage is 0.001 to 10 mg/day, preferable is 0.01 to 4 mg/day, and more preferable is 0.05 to 2mg/day.
- N.N-dicyclohexylcarbodiimide (10.83 g, 52.5 mmol), N-hydroxybenzotriazole (2.03 g, 15 mmol) and triethylamine (7.7 ml, 55.2 mmol) were added to a solution (130 ml) of N-(tert-butoxycarbonyl)-3-(thiazol-4-yl)-L-alanine (1) (13.62 g, 50 mmol) obtained by the method described in literatures (J. Am. Chem. Soc. 73, 2935 (1951) and Chem. Pharm. Bull.
- Step 3 l-[N-[(4S,5S)-(5-methyl-2-oxooxazolidin-4-yl)carbonyl]-3-(thiazol-4-yl)-L-alanyl-(2R)-2- methylpyrrolidine trihydrate (I- 1) Step 3 (1) Method A
- IR(Nujor)cm” 1 3517, 3342, 3276, 3130, 3092, 3060, 1754, 1682, 1610, 1551, 1465, 1442,
- Rolling Mouse Nagoya a hereditary ataxia mouse, is known as a model mouse for spinocerebellar ataxia and has been reported in many papers (E. Kurihara, N. Fukuda,
- Patent Literature 1 The following compounds in Patent Literature 1 and Non-Patent Literature 1 were used as Control Compounds 1 and 2.
- Each of the compounds was dissolved in a physiological saline on the day of the experiment.
- Each compound was orally administered to mice using a sonde for oral administration at the following dosage; Compound (I-l):l mg/kg and 3 mg/kg, Control Compound 1: 30 mg/kg and 100 mg/kg, Control Compound 2: 100 mg/kg and 300 mg/kg.
- Physiological saline alone was administered to mice as a control group.
- Volume for oral administration was 0.2 mL per 20 g body weight of a mouse.
- Ara-C 60mg/kg, Nippon Shinyaku was subcutaneously administered to Sprauge-Dawley rats (CLEA Japan, Inc) of 2 days old and 3 days old, and the effects of improving ataxia on Compound (1-1), Control Compound 1 and Control Compound 2 at 4 weeks old were investigated.
- Each of the compounds was dissolved in a physiological saline on the day of administration.
- Each compound was orally administered to rats using a sonde for oral administration at the following dosage; Compound (1-1): 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg and 3 mg/kg, Control Compound 1: 30mg/kg and 100mg/kg, Control Compound 2: 100 mg/kg and 300mg/kg.
- Physiological saline alone was administered to rats as a control group. The compounds were repetitively orally administered one a day for seven days and the effect was investigated 24 hours after the final administration.
- Volume for oral administration was 0.1 mL per 100 g body weight of a rat. Sample numbers were 5 or more in every group.
- Control Compound 1 has the same level efficacy as 1/300 dosage of Compound (1-1) and Control Compound 2 has the same level efficacy as 1/1000 or less dosage of Compound (1-1). Therefore, the results show Compound (1-1) has the excellent effect of improving ataxia.
- Control Compound 2 on ataxia on Rolling Mouse Nagoya were investigated.
- Granules are prepared using the following ingredients. Compound (I) 10 mg
- Compound (I) and lactose are made pass through a 60 mesh sieve.
- Corn starch is made pass through a 120 mesh sieve. They are mixed by a V-type mixer.
- An aqueous solution of HPC-L (low mucosity hydroxypropylcellulose) is added to the mixture and the resulting mixture is kneaded, granulated (by the extrusion with pore size 0.5 to 1 mm mesh), and dried.
- the dried granules thus obtained are sieved by a vibrating sieve (12/60 mesh) to yield the granules.
- Powders for filling capsules are prepared using the following ingredients.
- Compound (I) and lactose are made pass through a 60 mesh sieve.
- Corn starch is made pass through a 120 mesh sieve.
- an aqueous solution of HPC-L is added to the mixture and the resulting mixture is kneaded, granulated, and dried. Size of the dried granules thus obtained is regulated, 150 mg of them are filled into a No. 4 hard gelatin capsule.
- Tablets are prepared using the following ingredients.
- the compounds of the present invention can be an useful medicament for treating spinocerebellar ataxia or multiple system atrophy, or for improving ataxia or equilibrium disturbance.
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/662,182 US8071633B2 (en) | 2004-09-09 | 2005-09-08 | Pharmaceutical composition for treating spinocerebellar ataxia |
EP05783401.2A EP1786423B1 (en) | 2004-09-09 | 2005-09-08 | A pharmaceutical composition for treating ataxia, multiple system atrophy or balance disorders |
CA2579720A CA2579720C (en) | 2004-09-09 | 2005-09-08 | A pharmaceutical composition for treating ataxia, multiple system atrophy or balance disorders |
JP2007508661A JP5196641B2 (en) | 2004-09-09 | 2005-09-08 | Spinal cerebellar degeneration treatment |
ES05783401T ES2727452T3 (en) | 2004-09-09 | 2005-09-08 | Pharmaceutical composition to treat ataxia, multisystemic atrophy or balance disorders |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2004261977 | 2004-09-09 | ||
JP2004-261977 | 2004-09-09 | ||
US61371704P | 2004-09-29 | 2004-09-29 | |
US60/613,717 | 2004-09-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2006028277A1 true WO2006028277A1 (en) | 2006-03-16 |
Family
ID=35276461
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2005/016994 WO2006028277A1 (en) | 2004-09-09 | 2005-09-08 | A pharmaceutical composition for treating ataxia, multiple system atrophy or balance disorders |
Country Status (5)
Country | Link |
---|---|
US (1) | US8071633B2 (en) |
EP (1) | EP1786423B1 (en) |
CA (1) | CA2579720C (en) |
TW (1) | TWI350754B (en) |
WO (1) | WO2006028277A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107735089A (en) * | 2015-06-26 | 2018-02-23 | 橘生药品工业株式会社 | The dosage regimen of ataxic therapeutic agent in spinal cerebellar degeneration disease |
CN110691593A (en) * | 2017-06-02 | 2020-01-14 | 富士胶片富山化学株式会社 | Preventive or therapeutic agent for spinocerebellar degeneration |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3056210B1 (en) | 2013-10-11 | 2022-05-11 | National University Corporation Tokyo Medical and Dental University | Drug for prevention or treatment of spinocerebellar degeneration |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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JPS59155346A (en) * | 1983-02-24 | 1984-09-04 | Itsuro Sofue | Peptide |
EP0384380A2 (en) * | 1989-02-21 | 1990-08-29 | Japan Tobacco Inc. | Novel peptide derivatives and their pharmaceutical use |
WO1998008867A1 (en) * | 1996-08-28 | 1998-03-05 | Shionogi & Co., Ltd. | Novel peptide derivatives having thiazolyl-alanine residue |
WO1999053941A1 (en) * | 1998-04-15 | 1999-10-28 | Shionogi & Co., Ltd. | Oral preparations containing trh derivatives |
WO2002017954A1 (en) * | 2000-08-31 | 2002-03-07 | Shionogi & Co., Ltd. | Antiparkinsonism drugs |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS60190795A (en) | 1984-03-09 | 1985-09-28 | Takeda Chem Ind Ltd | Peptide |
JPS6133197A (en) | 1984-07-10 | 1986-02-17 | Tanabe Seiyaku Co Ltd | Dihydroorotic acid derivative and preparation thereof |
JPH0681753B2 (en) | 1987-05-21 | 1994-10-19 | 山之内製薬株式会社 | Treatment for spinocerebellar degeneration |
US5686420A (en) * | 1987-06-05 | 1997-11-11 | Georgetown University | Thyrotropin-releasing hormone analogs and method of use |
US5151497A (en) | 1989-02-21 | 1992-09-29 | Japan Tobacco Inc. | Histidyl peptide derivatives |
JPH09157286A (en) | 1995-10-06 | 1997-06-17 | Takeda Chem Ind Ltd | Tan-2335-related compound, its production and use thereof |
US6319902B1 (en) | 1997-08-22 | 2001-11-20 | Shionogi & Co., Ltd. | Peptide derivatives having thiazolyl-alanine residue |
ES2262322T3 (en) | 1998-06-10 | 2006-11-16 | Meiji Seika Kaisha, Ltd. | TREATMENT OF SPINOCEREBERAL DEGENARATION AND USEFUL COMOPOSITIONS FOR THE TREATMENT OF SPINOCEREBELAR DEGENERATION. |
WO2002004016A1 (en) | 2000-07-11 | 2002-01-17 | Shionogi & Co., Ltd. | Enteric preparations containing physiologically active peptides |
-
2005
- 2005-09-07 TW TW094130636A patent/TWI350754B/en active
- 2005-09-08 WO PCT/JP2005/016994 patent/WO2006028277A1/en active Application Filing
- 2005-09-08 EP EP05783401.2A patent/EP1786423B1/en not_active Not-in-force
- 2005-09-08 CA CA2579720A patent/CA2579720C/en active Active
- 2005-09-08 US US11/662,182 patent/US8071633B2/en active Active
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS59155346A (en) * | 1983-02-24 | 1984-09-04 | Itsuro Sofue | Peptide |
EP0384380A2 (en) * | 1989-02-21 | 1990-08-29 | Japan Tobacco Inc. | Novel peptide derivatives and their pharmaceutical use |
JPH03236397A (en) * | 1989-02-21 | 1991-10-22 | Japan Tobacco Inc | New peptide derivative |
WO1998008867A1 (en) * | 1996-08-28 | 1998-03-05 | Shionogi & Co., Ltd. | Novel peptide derivatives having thiazolyl-alanine residue |
EP0933379A1 (en) * | 1996-08-28 | 1999-08-04 | Shionogi & Co., Ltd. | Novel peptide derivatives having thiazolyl-alanine residue |
WO1999053941A1 (en) * | 1998-04-15 | 1999-10-28 | Shionogi & Co., Ltd. | Oral preparations containing trh derivatives |
WO2002017954A1 (en) * | 2000-08-31 | 2002-03-07 | Shionogi & Co., Ltd. | Antiparkinsonism drugs |
EP1321151A1 (en) * | 2000-08-31 | 2003-06-25 | Shionogi & Co., Ltd. | Antiparkinsonism drugs |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107735089A (en) * | 2015-06-26 | 2018-02-23 | 橘生药品工业株式会社 | The dosage regimen of ataxic therapeutic agent in spinal cerebellar degeneration disease |
US20180147189A1 (en) * | 2015-06-26 | 2018-05-31 | Kissei Pharmaceutical Co., Ltd. | Administration regimen for therapeutic agents for ataxia in spinocerebellar degeneration |
EP3315128A4 (en) * | 2015-06-26 | 2019-02-20 | Kissei Pharmaceutical Co., Ltd. | Dosing regimen of therapeutic agent for ataxia associated with spinocerebellar degeneration |
CN110691593A (en) * | 2017-06-02 | 2020-01-14 | 富士胶片富山化学株式会社 | Preventive or therapeutic agent for spinocerebellar degeneration |
CN110691593B (en) * | 2017-06-02 | 2023-05-02 | 富士胶片富山化学株式会社 | Preventive or therapeutic agent for spinocerebellar degeneration |
Also Published As
Publication number | Publication date |
---|---|
TW200616614A (en) | 2006-06-01 |
CA2579720C (en) | 2013-07-30 |
EP1786423B1 (en) | 2019-03-13 |
US20080027116A1 (en) | 2008-01-31 |
TWI350754B (en) | 2011-10-21 |
US8071633B2 (en) | 2011-12-06 |
CA2579720A1 (en) | 2006-03-16 |
EP1786423A1 (en) | 2007-05-23 |
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